title: Immunologic effects of omalizumab in children with severe refractory atopic dermatitis: a randomized, placebo-controlled clinical trial.
abstract: BACKGROUND
  Severe refractory atopic dermatitis (AD) is a chronic, debilitating condition that is associated with elevated serum immunoglobulin E (IgE) levels. Thymic stromal lymphopoietin (TSLP), thymus and activation-regulated chemokine (TARC) and OX40 ligand (OX40L) are important immunologic factors involved in the pathogenesis of AD. Omalizumab, an anti-IgE antibody indicated for use in allergic asthma, is implicated in regulating allergen presentation by dendritic cells and the T cell response during the effector phases of allergic disease. We investigated if anti-IgE therapy modulates the allergen-specific responses mediated by the TSLP pathway in young patients with severe refractory AD.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled study of 8 patients between the ages of 4 and 22 years (mean = 11.6 years) with severe refractory AD (clinical trials.gov NCT01678092). Serum IgE ranged from 218 to 1,890 (mean = 1,068 IU/ml). Subjects received omalizumab (n = 4) or placebo (n = 4) every 2-4 weeks over 24 weeks using a regimen extrapolated from the package insert. TSLP, TARC, OX40L and other cytokines involved in AD were measured by using cytometric bead arrays.
  
  
  RESULTS
  All patients receiving omalizumab had strikingly decreased levels of TSLP, OX40L, TARC (involved in Th2 polarization) and interleukin (IL)-9 compared to placebo. In addition, there was a marked increase in IL-10, a tolerogenic cytokine, in the omalizumab-treated group. Patients on anti-IgE therapy had an improvement in clinical outcomes as measured by the SCORAD system; however, these effects were comparable to improvements in the control group.
  
  
  CONCLUSIONS
  Anti-IgE therapy with omalizumab decreases levels of cytokines that are involved in Th2 polarization and allergic inflammation, including TSLP, TARC and OX40L.
authors.affiliation: Division of Pediatric Allergy, Massachusetts General Hospital, Boston, Mass., USA.
authors.forename: Shuba Rajashri
authors.initials: SR
authors.lastname: Iyengar
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Hoyte
authors.forename: Angelica
authors.initials: A
authors.lastname: Loza
authors.forename: Salvatore
authors.initials: S
authors.lastname: Bonaccorso
authors.forename: David
authors.initials: D
authors.lastname: Chiang
authors.forename: Dale T
authors.initials: DT
authors.lastname: Umetsu
authors.forename: Kari Christine
authors.initials: KC
authors.lastname: Nadeau
mesh_terms: D000293:Adolescent; D018926:Anti-Allergic Agents / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D000069444:Omalizumab; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; C026408:anti-IgE antibodies; D000069444:Omalizumab; D007073:Immunoglobulin E